Shiuan Chen, Ph.D.
- Chemoprevention Research Program
- Breast Cancer Translational Research
- Program in Natural Therapies
- 2012 - present, Chair, Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA
- 2009 - 2012, Director and Professor, Division of Tumor Cell Biology, Beckman Research Institute of City of Hope, Duarte, CA
- 2009 - 2012, Associate Chair, Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA
- 2002 - 2009, Professor and Director, Division of Tumor Cell Biology, Department of Surgery, City of Hope, Duarte, CA
- 1994 - 2002, Professor, Department of Immunology, Beckman Research Institute of City of Hope, Duarte, CA
- 1988 - 1994, Associate Research Scientist, Department of Immunology, Beckman Research Institute of City of Hope, Duarte, CA
- 1985 - 1988, Assistant Research Scientist, Department of Immunology, Beckman Research Institute of City of Hope, Duarte, CA
- 1982 - 1985, Research Assistant Professor, School of Pharmacy, University of Southern California, Los Angeles, CA
- 1981 - 1982, Assistant Researcher, Department of Biochemistry and Biophysics, University of Hawaii
- 1978 - 1981, Junior Researcher, Department of Biochemistry and Biophysics, University of Hawaii
- Cancer Biology
- Program in Natural Therapies
- University of Hawaii, Honolulu, Hawaii, Ph.D., Biochemistry
- National Taiwan College of Marine Science and Technology, Keelung Taiwan, Republic of China, B.S., Chemistry
There are many factors which can impact the chances of developing breast cancer. Alongside risks such as previous personal or familial history with breast cancer, genetic predisposition or high breast density; there are also so called “lifestyle” risks for developing breast cancer. Exposure to environmental pollutants and toxic chemicals are also possible risk factors for breast cancer.
Only one environmental factor is known to increase breast cancer risk and that factor is exposure to ionizing radiation. Any increase in breast cancer risk associated with exposure to environmental pollutants will likely depend on the amount and type of exposure, the age when the exposure occurs and the properties of the pollutant.
Our study focuses on women being exposed to two such exposures during the menopausal transition and how this exposure may impact a woman’s risk of breast cancer. The two environmental pollutants, both of which are widespread in the environment today, are polybrominated diphenyl ethers and bisphenol A.
The goal of the study is to better understand the risks associated with certain environmental pollutants and to help promote women’s health.
Breast Cancer Translation Research
Shiuan Chen, Ph.D., was one of the three investigators who originally isolated the full-length human aromatase cDNA clones. Aromatase is an enzyme that converts androgen to estrogen. Aromatase inhibitors (AIs) are important drugs to treat estrogen-dependent breast cancer. Approximately 60 percent of premenopausal and 75 percent of postmenopausal breast cancer patients have estrogen-dependent carcinomas.
Since aromatase is the enzyme responsible for the synthesis of estrogen, and estrogen can have a major effect in the development of breast cancer, an abnormal expression of aromatase in breast cancer cells and/or surrounding adipose stromal cells may have a significant influence on breast tumor development and growth in cancer patients. Aromatase is expressed at higher levels in human breast cancer tissue than in normal breast tissue, as measured by various biochemical assays. During the last 15 years, aromatase inhibitors (AIs) have been demonstrated to be superior to tamoxifen for the treatment of hormonal dependent breast cancer. While this new generation of aromatase inhibitors is shown to be useful in the treatment of hormonal responsive breast cancer, resistance to such endocrine therapy still develops. Through collaboration with Yate-Ching Yuan, Ph.D., (Bioinformatics), we are carrying out gene expression array experiments on AI-responsive as well as resistant cell lines that have been generated in our laboratory. We are identifying and functionally confirming the roles of genes involved in resistance.
These studies will produce valuable molecular information regarding the mechanisms of AI resistance, and the information will help design approaches to reduce resistance and improve the efficacy of AI treatments of breast cancer. Furthermore, our model systems are valuable to test new drugs against endocrine therapy resistance. We are working with several medical and translational research colleagues (Joanne Mortimer, M.D. , Yuan Yuan, M.D., Ph.D., George Somlo, M.D., Laura Kruper, M.D., Courtney Vito, M.D.,Paul Frankel, Ph.D., Tim Synold, Pharm.D., and Ned Newman, Ph.D.) to carry preclinical studies in our laboratories and then to design new therapeutic approaches to treat AI resistant breast cancer.
Chemoprevention and Superfood Research Program
Since the summer of 2004, Chen and 27 other investigators have initiated an effort to develop a Chemoprevention Research Program at City of Hope. Through biweekly meetings, these Beckman Research Institute of City of Hope researchers and clinicians exchange research information and ideas. Four research areas have recently been chosen to focus on. The immediate goal is to generate preliminary results in these new target areas that will lead to the development of multidiscipline translational chemoprevention research projects at our institution.
Our laboratory has found that grapes, mushrooms and pomegranate contain chemicals that can suppress aromatase activity. Therefore, a diet containing these "superfoods" would be considered preventative against breast cancer. We are purifying and characterizing these natural anti-aromatase chemicals and evaluating their in vivo effects using animal experiments. The active chemicals in grapes have been found to be procyanidin dimers that are present at high concentrations in grape seeds. Melanie Palomares, M.D., M.S., Jeffrey Weitzel, M.D., (Clinical Cancer Genomics), Tim Synold, Pharm.D., (Immuno-Oncology) and this laboratory have collaborated and initiated a grape seed extract clinical trial and a mushroom clinical trial based on the chemoprevention studies against breast cancer performed in our laboratory. In addition, experiments have been carried out to show that blueberry contains phytochemicals that can suppress the proliferation and migration of triple negative breast cancer in cell culture and animals.
Furthermore, we have found that mushrooms contain chemicals that act as inhibitors of steroid 5-alpha reductase. Androgen plays a critical role in prostate cancer development. In the prostate, testosterone (an androgen) is converted to dihydrotestosterone (DHT), an androgen that is even more potent than testosterone. This conversion is catalyzed by the enzyme steroid 5-alpha reductase. An elevation of the steroid 5-alpha reductase activity in the prostate may cause benign prostate hyperplasia (a common problem in older men) and also promote the growth of prostate cancer. Animal experiments have been performed to evaluate the use of these phytochemicals as drugs in the prevention and/or treatment of prostate cancer. One clinical trial designed, based Chen’s findings, is being carried out at City of Hope with Przemyslaw Twardowski, M.D. (Medical Oncology) to evaluate the protective effect of mushroom chemicals against PSA increase in prostate cancer patients. The trial has resulted in two patients with complete response, two patients with partial response, and eight patients with stable PSA response. A recent study in the Chen laboratory has revealed that the intake of mushrooms may reduce the incidence of metabolic diseases such as fatty liver and insulin resistance.
In 2014, with a $2.5 million gift from the Panda Charitable Foundation, a Program in Natural Therapies was established at City of Hope. This fund supports three lines of research to investigate natural products’ abilities to fight against cancer. Chen is investigating how the foods themselves can improve outcomes of treatment-resistance breast cancer. In addition, the Chen laboratory is generating patient-derived xenograft (PDX) models for novel treatment of breast cancer.
Endocrine Disruptor Research
We are also conducting research to determine how environmental chemicals modulate the activity and expression of aromatase in human tissue. Experiments are being conducted to provide a molecular and mechanistic basis as to how phytochemicals and organochlorine compounds affect estrogen biosynthesis (e.g., aromatase function) in women. Research from Chen’s and other laboratories have revealed that estrogen receptors (ER), aromatase, and ERR are key players in breast cancer promotion and in cancer recurrence following endocrine treatment. Furthermore, proof-of-concept studies have revealed that these proteins are targets of endocrine disruptors. Based on these observations, we hypothesize that environmental chemicals will play critical roles in modulating breast cancer through ER, aromatase and ERR. We have developed a high throughput screening system (AroER Tri-Screen™) for identifying chemicals targeting ER and aromatase. The goal of this research is to develop screening assays for identifying and testing chemicals with relevance to known and suspected causes of estrogen-dependent breast cancer. Our collaborators include Yate-Ching Yuan, Ph.D. (Bioinformatics Core), Xiwei Wu, M.D., Ph.D. (Integrative Genomics Core), Christina Teng, Ph.D. (National Institute of Environmental Health Sciences), Menghang Xia, Ph.D., and Ruiling Huang, Ph.D. (National Center for Advancing Translational Sciences), Sandra Finestone, Psy.D. (Hope Wellness Center, Costa Mesa, California) and Kimlin Tam Ashing, Ph.D. (Population Sciences). Furthermore, we are collaborating with Myrto Petreas, Ph.D. (California Department of Toxic Substances Control) and Peggy Reynolds, Ph.D. (Cancer Prevention Institute of California) for the evaluation of estrogenic activity in human serum using AroER Tri-Screen.
Research Associate I
Kohei Saeki, Ph.D.
Xiaoqiang Wang, Ph.D.
Yuan-Zhong Wang, Ph.D.
February 16, 2017
August 04, 2016
June 21, 2016
Information listed here is obtained from PubMed, a public database. City of Hope is not responsible for its accuracy. Selected Peer-reviewed Publications (Selected from 249 peer reviewed publications)
Petrossian K, Kanaya, N, Lo C, Hsu PY, Nguyen D, Yang L, Yang L, Warden C, WuX, Pillai R, Bernal L, Huang CS, Kruper L, Yuan Y, Somlo G, Mortimer J, Chen S. ER-mediated cell cycle progression is an important requisite for CDK4/6 inhibitor response in HR+ breast cancer. Oncotarget. 2018; 9(45):27736-27751. Doi: 10.18632/oncotarget.25552. PubMed [journal] PMID: 29963233 PMCID: PMC6021239
Petrossian K, Nguyen D, Lo C, Kanaya N, Somlo G, Cui YX, Huang CS, Chen S. Use of dual mTOR inhibitor MLN0128 against everolimus-resistant breast cancer. Breast cancer research and treatment. 2018; 70(3):499-506. NIHMSID: NIHMS957500 PubMed [journal] PMID: 29623577, PMCID: PMC6026053
Lynch C, Zhao J, Huang R, Kanaya N, Bernal L, Hsieh JH, Auerbach SS, Witt KL, Merrick BA, Chen S, Teng CT, Xia M. Identification of Estrogen-Related Receptor αAgonists in the Tox21 Compound Library. Endocrinology. 2018; 159(2):744-753. PubMed [journal] PMID: 29216352, PMCID: PMC5774247
Hsu PY, Wu VS, Kanaya N, Petrossian K, Hsu HK, Nguyen D, Schmolze D, Kai M, Liu CY, Lu H, Chu P, Vito CA, Kruper L, Mortimer J, Chen S. Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant. Clinical cancer research: an official journal of the American Association for Cancer Research. 2018; 24(2):395-406. PubMed [journal] PMID: 29079660
Liu CY, Wu CY, Petrossian K, Huang TT, Tseng LM, Chen S. Treatment for the endocrine resistant breast cancer: Current options and future perspectives. The Journal of steroid biochemistry and molecular biology. 2017; 172:166-175. PubMed [journal] PMID: 28684381
Kanaya N, Somlo G, Wu J, Frankel P, Kai M, Liu X, Wu SV, Nguyen D, Chan N, Hsieh MY, Kirschenbaum M, Kruper L, Vito C, Badie B, Yim JH, Yuan Y, Hurria A, Peiguo C, Mortimer J, Chen S. Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. The Journal of steroid biochemistry and molecular biology. 2017; 170:65-74. NIHMSID: NIHMS785187 PubMed [journal] PMID: 27154416, PMCID: PMC5094906
Wang Y, Zhou D, Phung S, Warden C, Rashid R, Chan N, Chen S. SGK3 sustains ERα signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis. Proceedings of the National Academy of Sciences of the United States of America. 2017; 114(8):E1500-E1508. PubMed [journal] PMID: 28174265, PMCID: PMC5338386
Cao H, Mu Y, Li X, Wang Y, Chen S, Liu JP. A Systematic Review of Randomized Controlled Trials on Oral Chinese Herbal Medicine for Prostate Cancer. PloS one. 2016; 11(8):e0160253. PubMed [journal] PMID: 27490098, PMCID: PMC4973922
Chan HJ, Petrossian K, Chen S. Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells. The Journal of steroid biochemistry and molecular biology. 2016; 161:73-83. NIHMSID: NIHMS722586 PubMed [journal] PMID: 26277097, PMCID: PMC4752924
Chen S, Hsieh JH, Huang R, Sakamuru S, Hsin LY, Xia M, Shockley KR, Auerbach S, Kanaya N, Lu H, Svoboda D, Witt KL, Merrick BA, Teng CT, Tice RR. Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library. Toxicological sciences: an official journal of the Society of Toxicology. 2015; 147(2):446-57. PubMed [journal] PMID: 26141389, PMCID: PMC4592355
Chan HJ, Li H, Liu Z, Yuan YC, Mortimer J, Chen S. SERPINA1 is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients. Oncotarget. 2015; 6(28):25815-27. PubMed [journal] PMID: 26158350, PMCID: PMC4694868
Wu VS, Kanaya N, Lo C, Mortimer J, Chen S. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer? The Journal of steroid biochemistry and molecular biology. 2015; 153:45-53. NIHMSID: NIHMS692645 PubMed [journal] PMID: 25998416, PMCID: PMC4568143
Twardowski P, Kanaya N, Frankel P, Synold T, Ruel C, Pal SK, Junqueira M, Prajapati M, Moore T, Tryon P, Chen S. A phase I trial of mushroom powder in patients with biochemically recurrent prostate cancer: Roles of cytokines and myeloid-derived suppressor cells for Agaricus bisporus-induced prostate-specific antigen responses. Cancer. 2015; 121(17):2942-50. NIHMSID: NIHMS869874 PubMed [journal] PMID: 25989179, PMCID: PMC5685188
Chen Z, Yuan YC, Wang Y, Liu Z, Chan HJ, Chen S. Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer. Breast cancer research and treatment. 2015; 152(1):29-39. NIHMSID: NIHMS696192 PubMed [journal] PMID: 26026468, PMCID: PMC4470793
Kai M, Kanaya N, Wu SV, Mendez C, Nguyen D, Luu T, Chen S. Targeting breast cancer stem cells in triple-negative breast cancer using a combination of LBH589 and salinomycin. Breast cancer research and treatment. 2015; 151(2):281-94. NIHMSID: NIHMS723944 PubMed [journal] PMID: 25904215, PMCID: PMC4587767
Kanaya N, Nguyen DM, Lu H, Wang YZ, Hsin LY, Petreas M, Nelson D, Guo W, Reynolds P, Synold T, Chen S. AroER tri-screen™ is a novel functional assay to estimate both estrogenic and estrogen precursor activity of chemicals or biological specimens. Breast cancer research and treatment. 2015; 151(2):335-45. NIHMSID: NIHMS723943 PubMed [journal] PMID: 25962693, PMCID: PMC4591046
Chen Z, Wang Y, Warden C, Chen S. Cross-talk between ER and HER2 regulates c-MYC-mediated glutamine metabolism in aromatase inhibitor resistant breast cancer cells. The Journal of steroid biochemistry and molecular biology. 2015; 149:118-27. NIHMSID: NIHMS663846 PubMed [journal] PMID: 25683269, PMCID: PMC4380584
Chen Z, Wang O, Nie M, Elison K, Zhou D, Li M, Jiang Y, Xia W, Meng X, Chen S, Xing X. Aromatase deficiency in a Chinese adult man caused by novel compound heterozygous CYP19A1 mutations: effects of estrogen replacement therapy on the bone, lipid, liver and glucose metabolism. Molecular and cellular endocrinology. 2015; 399:32-42. NIHMSID: NIHMS636635 PubMed [journal] PMID: 25301327, PMCID: PMC4457386
Li F, Wong TY, Lin SM, Chow S, Cheung WH, Chan FL, Chen S, Leung LK. Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole. The Journal of pharmacology and experimental therapeutics. 2014; 351(2):270-7. PubMed [journal] PMID: 25138022
Wong TY, Li F, Lin SM, Chan FL, Chen S, Leung LK. Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor growth in mice. BMC cancer. 2014; 14:426. PubMed [journal] PMID: 24923427, PMCID: PMC4070644
Wang Y, Wong TY, Chan FL, Chen S, Leung LK. Assessing the effect of food mycotoxins on aromatase by using a cell-based system. Toxicology in vitro: an international journal published in association with BIBRA. 2014; 28(4):640-6. PubMed [journal] PMID: 24512813
Wang Y, Zhou D, Chen S. SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation through activation of p70 S6 kinase and up-regulation of cyclin D1. Molecular endocrinology (Baltimore, Md.). 2014; 28(6):935-48. PubMed [journal] PMID: 24739041, PMCID: PMC4042072
Chen S, Zhou D, Hsin LY, Kanaya N, Wong C, Yip R, Sakamuru S, Xia M, Yuan YC, Witt K, Teng C. AroER tri-screen is a biologically relevant assay for endocrine disrupting chemicals modulating the activity of aromatase and/or the estrogen receptor. Toxicological sciences: an official journal of the Society of Toxicology. 2014; 139(1):198-209. PubMed [journal] PMID: 24496634, PMCID: PMC4038786
Wang Y, Xu W, Zhou D, Neckers L, Chen S. Coordinated regulation of serum- and glucocorticoid-inducible kinase 3 by a C-terminal hydrophobic motif and Hsp90-Cdc37 chaperone complex. The Journal of biological chemistry. 2014; 289(8):4815-26. PubMed [journal] PMID: 24379398, PMCID: PMC3931044
Kanaya N, Adams L, Takasaki A, Chen S. Whole blueberry powder inhibits metastasis of triple negative breast cancer in a xenograft mouse model through modulation of inflammatory cytokines. Nutrition and cancer. 2014; 66(2):242-8. PubMed [journal] PMID: 24364759
Kanaya N, Vonderfecht S, Chen S. Androgen (dihydrotestosterone)-mediated regulation of food intake and obesity in female mice. The Journal of steroid biochemistry and molecular biology. 2013; 138:100-6. NIHMSID: NIHMS604184 PubMed [journal] PMID: 23665441, PMCID: PMC4130703
Warden CD, Kanaya N, Chen S, Yuan YC. BD-Func: a streamlined algorithm for predicting activation and inhibition of pathways. PeerJ. 2013; 1:e159. PubMed [journal] PMID: 24058887, PMCID: PMC3775632
For my complete list of published works, see my bibliography: https://www.ncbi.nlm.nih.gov/pubmed?cmd=Link&LinkName=pubmed_pubmed&from_uid=28174265
- 2016, Ad hoc reviewer for the BMCT Study Section, NIH
- 2016, Ad hoc reviewer for the Molecular and Cellular Endocrinology Study Section, NIH
- 2010, Member of the Breast Cancer and the Environment Study Section, NIEHS
- 2008-2012, Member of the Molecular and Cellular Endocrinology Study Section, NIH
- 2006, Programmatic review for the DOD Breast Cancer Research Program
- 2006, Reviewer for applications for the Tumor Microenvironment Network, NIH
- 2006 - present, Section Editor, Journal of Molecular Signaling
- 2006, Reviewer for the Mouse Metabolic Phenotyping Centers Consortium, NIH
- 2004, Reviewer for the botanical center grant applications, NIH
- 2003-2005, Member of the Tumor Cell Biology Study Section, NIH
- 2002-2003, Member of the Metabolic Pathology Study Section, NIH
- 2002-Present, Corresponding Editor, The Journal of Steroid Biochemistry and Molecular Biology
- 2002, Reviewer for the SCOR applications, NIH
- 2000-Present, Member of Special Emphasis Panels, NIH
- 2000-2001, Chairman of the Student Research Committee, American Heart Association, Western States Affiliate
- 1999-2000, Member of the Study Section for Insight Award for Breast Cancer, NIH
- 1998-1999, U.S. Environmental Protection Agency, Endoctrine Disruptor Study Section
- 1998-2002, Member of the Research Committee, American Heart Association, Western States Affiliate
- 1996-1998, 2001-2003, 2005, Member of the Study Sections of the US Army Breast Cancer Research Program
- 1996-2000, Member of the Reproductive Endocrinology Study Section, NIH
- 1985-Present, Member of the City of Hope Cancer Center